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Multi-center Study of Myeloablative Allo Stem Cell Transplant for Non-remission AML Using CloBu4 Regimen (CloBu4)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01457885
Recruitment Status : Completed
First Posted : October 24, 2011
Results First Posted : July 25, 2016
Last Update Posted : June 2, 2017
Genzyme, a Sanofi Company
Otsuka Pharmaceutical Development & Commercialization, Inc.
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Brief Summary:

Although transplant results for AML in complete remission (CR) at the time of transplant have improved, transplant results for non-remission AML have been quite poor. Most multi-center studies have focused on standard risk AML patients and not many studies have been done in this population of patients with non-remission AML. There are a large number of older patients with non-remission AML because the complete remission rate with induction chemotherapy decreases with age. Such older patients do not tolerate conventional full intensity conditioning regimens. Thus, an effective and tolerable conditioning regimen for non-remission AML is a great unmet need for current transplant practice.

From the investigators earlier study, it is suggested that replacing Fludarabine of standard FluBu4 regimen by Clofarabine (a related drug with much more potent anti-leukemia effect) in the transplant conditioning regimen may potentiate the anti-tumor activity of the conditioning regimen without adding significant toxicity, a goal of new conditioning regimen development.

The investigators expect to enroll a total of 75 patients from about fifteen sites. The investigators main objective is to confirm both the safety and efficacy as measured by one-year overall survival, of the CloBu4 combination as full intensity conditioning for non-remission acute myelogenous leukemia.

Condition or disease Intervention/treatment Phase
Acute Myeloblastic Leukemia Drug: Clofarabine/Busulfan x 4 Procedure: Peripheral blood stem cell transplant Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 75 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multi-center Single Arm Phase II Study of Myeloablative Allogeneic Stem Cell Transplantation for Non-remission Acute Myeloblastic Leukemia (AML) Using Clofarabine and Busulfan x 4 (CloBu4) Regimen
Study Start Date : November 2011
Actual Primary Completion Date : November 2014
Actual Study Completion Date : June 14, 2016

Arm Intervention/treatment
Experimental: CloBu4 regimen
After pre-conditioning with CloBu4 (Clofarabine/Busulfan x 4), subjects will receive a peripheral blood stem cell transplant
Drug: Clofarabine/Busulfan x 4
  • Clofarabine IV dose level: 40 mg/m2/day x 5 days
  • Busulfan IV dose level: 3.2 mg/kg daily x 4 days

Procedure: Peripheral blood stem cell transplant
Peripheral blood stem cell transplant, after pre-conditioning drug treatment

Primary Outcome Measures :
  1. Cumulative Incidence of Non Relapse Mortality (NRM) [ Time Frame: 1 year ]
    Percentage of patients passed without relapse/recurrence at 1 year.

Secondary Outcome Measures :
  1. The Percentage of Patients Alive at 1 Year [ Time Frame: 1 year ]
    Overall survival was calculated following transplant using a CloBu4 conditioning regimen for patients with non-remission AML

  2. Incidence of Relapse [ Time Frame: 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Disease Criteria

  • AML not in remission at the time of transplant

    • "Not in remission" is defined as "greater than 5.0% bone marrow blasts by aspirate morphology," as determined by a bone marrow aspirate obtained within 2 weeks of study registration.
    • For primary induction failure patients: Patients must have failed at least 2 induction regimens.
    • For patients with relapsed disease: Patients who relapse more than 6 months after preceding remission must fail at least one reinduction regimen to be eligible. For patients in whom the preceding remission is equal to or shorter than 6 months duration, no re-induction regimen is required to qualify for this protocol.
  • If the pre-transplant bone marrow aspirate and biopsy are hypoplastic (less than 10% cellularity), and blast percentages cannot be determined, the patient is eligible if the preceding bone marrow met the above criteria.
  • Patients with peripheral circulating blasts or patients with extramedullary leukemia are eligible if bone marrow aspirate and biopsy meets the above criteria. Age and Organ Function Criteria
  • Age: 2 to 65 years in age.
  • Cardiac: LVEF ≥ 40% by MUGA (Multi Gated Acquisition) scan or echocardiogram.
  • Pulmonary: FEV1 and FVC capacity) ≥ 40% predicted, DLCO (corrected for hemoglobin) ≥ 40% of predicted.
  • Children who are unable to cooperate for pulmonary function tests (PFTs), must have no evidence of dyspnea at rest, no exercise intolerance, and not require supplemental oxygen therapy.
  • Renal: Age equal to or older than 12: The estimated creatinine clearance (CrCl) must be equal or greater than 60 mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula. Age younger than 12: Either estimated or measured CrCl should be greater than 90 ml/min/1.73m2. For estimation, Schwartz formula will be used.
  • Hepatic: Serum bilirubin ≤ 1.5 x upper limit of normal (ULN); (AST)/ ALT ≤ 2.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN
  • Performance status: Karnofsky ≥ 70%., or Lansky≥70% Consent: All patients must sign informed consent

Exclusion Criteria:

  • Active life-threatening cancer requiring treatment other than AML
  • Non-compliant to medications.
  • No appropriate caregivers identified.
  • HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive
  • Active life-threatening cancer requiring treatment other than AML
  • Uncontrolled medical or psychiatric disorders.
  • Uncontrolled infections, defined as positive blood cultures within 72 hours of study entry, or evidence of progressive infection
  • Active central nervous system (CNS) leukemia
  • Preceding allogeneic HSCT
  • Receiving intensive chemotherapy within 21 days of registration.
  • Patients with preceding primary myelofibrosis
  • Peripheral blasts > 10,000/μL at the time of registration

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01457885

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United States, Alabama
University of Alabama, Birmingham
Birmingham, Alabama, United States, 35233
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Michigan
University of Michigan Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University at St Louis
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Vanderbuilt University
Nashville, Tennessee, United States, 37232
United States, Washington
University of Washington
Seattle, Washington, United States, 98109
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
Genzyme, a Sanofi Company
Otsuka Pharmaceutical Development & Commercialization, Inc.
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Study Chair: Shin Mineishi, MD University of Alabama at Birmingham
Principal Investigator: John M Magenau, MD University of Michigan, Department of Internal Medicine
Study Chair: Stephen J Forman, MD City of Hope National Medical Center
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Responsible Party: University of Michigan Rogel Cancer Center Identifier: NCT01457885    
Other Study ID Numbers: UMCC 2011.038
First Posted: October 24, 2011    Key Record Dates
Results First Posted: July 25, 2016
Last Update Posted: June 2, 2017
Last Verified: May 2017
Keywords provided by University of Michigan Rogel Cancer Center:
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic